Positive benefits of theophylline in a randomized, double-blind, parallel-group, placebo-controlled study of low-dose, slow-release theophylline in the treatment of COPD for 1 year

Respirology. 2006 Sep;11(5):603-10. doi: 10.1111/j.1440-1843.2006.00897.x.


Objective and background: Increasing evidence suggests that low-dose theophylline has anti-inflammatory benefits and is safe in the treatment of COPD. This study aims to evaluate the efficacy and safety of low-dose, slow-release oral theophylline administered over a 1-year period in patients with COPD.

Methods: A randomized, double-blind, parallel-group, placebo-controlled trial was carried out. In total, 110 participants with COPD were randomly assigned to receive slow-release theophylline (100 mg b.i.d.) or placebo for 1 year. Use of medicine and symptoms recorded by diary cards; pulmonary function, exacerbations of COPD, quality of life and the use of rescue medicine were evaluated. Superiority test was used to estimate the efficacy.

Results: Of 110 participants, 85 (77.3%) complied with the protocol, with 42 subjects in theophylline and 43 subjects on placebo. In both intention-to-treat and per-protocol population analysis, greater improvement in pre-bronchodilator FEV(1) (P = 0.038 and P = 0.070, respectively), lower frequency of COPD exacerbations (P = 0.047 and P = 0.035, respectively), fewer days of COPD exacerbations (P = 0.045 and P = 0.046, respectively), lower frequency of clinical visits (P = 0.017 and P = 0.039, respectively), greater improvement in satisfaction with treatment (P = 0.014 and P = 0.004, respectively) were found in the theophylline group than in the placebo group. In per-protocol population, greater improvements in quality of life (P = 0.047) were also observed in the theophylline group and the mean time to the first exacerbation was delayed in theophylline group in comparison with placebo group (P = 0.047). Drug-related adverse events such as stomach discomfort (3.51%), headache (3.51%), insomnia (1.75%) and palpitation (1.75%) were found in the theophylline group.

Conclusions: Low-dose, slow-release oral theophylline is effective and well-tolerated in the long term treatment of stable COPD, although it does not improve post-bronchodilator lung function.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Double-Blind Method
  • Dyspnea / drug therapy
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Quality of Life
  • Theophylline / administration & dosage*
  • Theophylline / adverse effects


  • Bronchodilator Agents
  • Theophylline